ArticleProceedings of the National Academy of Sciences of the United States of America2019
Trisomy 21 dysregulates T cell lineages toward an autoimmunity-prone state associated with interferon hyperactivity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
103 citing papers in PubMed, 3 syntheses or guidelines pooled it, 183 citations in OpenAlex.
- A systematic review of celiac disease recommendations for children with Down syndrome.Journal of pediatric gastroenterology and nutrition · 2026Pooled it
- Revisiting down syndrome through the lens of interferonopathy and innate immune dysregulation.Frontiers in immunology · 2026Pooled it
- Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome.Molecular medicine (Cambridge, Mass.) · 2020Pooled it
- Trial
- Clinical considerations for immune dysregulation and immunodeficiency in Down syndrome.Journal of human immunity · 2026Review
- Immune dysregulation in children with Down syndrome: clinical implications and emerging therapies.Current opinion in rheumatology · 2026Review
- Progressive deterioration of adaptive immune repertoires in Down syndrome linked to interferon hyperactivity and lymphoid tissue disorganization.bioRxiv : the preprint server for biology · 2026Article
- Immune Dysregulation in Down Syndrome: Implications for Infectious Susceptibility and Vaccine Response.Journal of clinical immunology · 2026Review
- How I Treat: Immune dysregulation in Down syndrome.Journal of human immunity · 2026Review
- Surveying immune and inflammatory alterations in periodontitis among individuals with Down syndrome: A preliminary cross-sectional study.Journal of periodontology · 2026Article
- Endocrine and Digestive Disorders Arising in Childhood in Down Syndrome and Their Cross-Talk.Nutrients · 2026Review
- Aberrant chromatin remodeling influences human neural cell fate change in Trisomy 21.bioRxiv : the preprint server for biology · 2026Article
- Vaccination in individuals with Down syndrome: immune vulnerability, safety, efficacy and opportunities.NPJ vaccines · 2026Review
- Systematic multi-omic deconvolution of the clinical heterogeneity of Down syndrome.Nature communications · 2026Article
- Trisomy 21 Drives ADARB1 Overexpression and Premature RNA Recoding in the Developing Fetal Brain.Nature communications · 2026Article
- Day/night variations of myeloid and lymphoid cell subsets in the murine inguinal lymph node.FEBS open bio · 2026Article
- Altered hepatic metabolism in Down syndrome.Cell reports · 2026Article
- Article
- Interferon receptor gene dosage differentially regulates hypoxia-induced platelet activation and pulmonary hypertension in down syndrome.Frontiers in immunology · 2026Article
- A novel clustering of down syndrome and coeliac disease complicated by enteritis and small intestinal strictures: a case series.Therapeutic advances in gastroenterology · 2026Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Trisomy 21 (T21) causes Down syndrome (DS), a condition characterized by high prevalence of autoimmune disorders. However, the molecular and cellular mechanisms driving this phenotype remain unclear. Building upon our previous finding that T cells from people with DS show increased expression of interferon (IFN)-stimulated genes, we have completed a comprehensive characterization of the peripheral T cell compartment in adults with DS with and without autoimmune conditions. CD8+ T cells from adults with DS are depleted of naïve subsets and enriched for differentiated subsets, express higher levels of markers of activation and senescence (e.g., IFN-γ, Granzyme B, PD-1, KLRG1), and overproduce cytokines tied to autoimmunity (e.g., TNF-α). Conventional CD4+ T cells display increased differentiation, polarization toward the Th1 and Th1/17 states, and overproduction of the autoimmunity-related cytokines IL-17A and IL-22. Plasma cytokine analysis confirms elevation of multiple autoimmunity-related cytokines (e.g., TNF-α, IL17A-D, IL-22) in people with DS, independent of diagnosis of autoimmunity. Although Tregs are more abundant in DS, functional assays show that CD8+ and CD4+ effector T cells with T21 are resistant to Treg-mediated suppression, regardless of Treg karyotype. Transcriptome analysis of white blood cells and T cells reveals strong signatures of T cell differentiation and activation that correlate positively with IFN hyperactivity. Finally, mass cytometry analysis of 8 IFN-inducible phosphoepitopes demonstrates that T cell subsets with T21 show elevated levels of basal IFN signaling and hypersensitivity to IFN-α stimulation. Therefore, these results point to T cell dysregulation associated with IFN hyperactivity as a contributor to autoimmunity in DS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.